title: Rhynchophylline-induced vasodilation in human mesenteric artery is mainly due to blockage of L-type calcium channels in vascular smooth muscle cells.
abstract: Rhynchophylline (Rhy) is a pharmacologically active substance isolated from Uncaria rhynchophylla which has been used to treat cardiovascular diseases and has drawn considerable attention in recent years for its antihypertensive activities. We investigated the actions of Rhy on endothelium-denuded human mesenteric artery by tension measurement and its actions on high conductance Ca(2+)-activated K(+) channels (BKCa) currents and calcium currents (ICa) in freshly isolated smooth muscle cells using perforated patch clamp technique. Intracellular Ca(2+) level was measured in Fura-2-loaded cells. Rhy inhibited both the KCl and BayK-evoked mesenteric artery constrictions in a dose-dependent manner. K(+) channel blockers (TEA, glibenclamide, IbTX, and 4-AP) did not affect the vasorelaxing effect of Rhy. Rhy inhibited L-type voltage-gated Ca(2+) current (ICa,L) but had no significant effect on macroscopic BKCa current. Rhy preincubation markedly reduced the elevation of [Ca(2+)]i level induced by KCl depolarization. Caffeine-stimulated [Ca(2+)]i elevation was also decreased to some extent by pretreatment with Rhy for 20 min. Our results show that Rhy relaxes smooth muscles of human mesenteric resistance arteries, mainly due to inhibition of Ca(2+) influx by blockage of L-type Ca(2+) channels and thereby the decrease in [Ca(2+)]i.
authors.affiliation: Department of Electrophysiology, Institute of Cardiovasology, Luzhou Medical College, Luzhou, Sichuan, 646000, China.
authors.forename: Peng-Yun
authors.initials: PY
authors.lastname: Li
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zeng
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Jing
authors.initials: J
authors.lastname: Wen
authors.forename: Isao
authors.initials: I
authors.lastname: Inoue
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000494:pharmacology*; D008638:Mesenteric Arteries / Q000166:cytology; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D000078183:Oxindoles; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D026121:Indole Alkaloids; D000078183:Oxindoles; D014665:Vasodilator Agents; C052714:rhyncophylline; D002118:Calcium